The Effect of Maternal Multiple Micronutrient Supplementation on Female Early Infant Mortality Is Fully Mediated by Increased Gestation Duration and Intrauterine Growth

Mary K Quinn; Emily R Smith; Paige L Williams; Willy Urassa; Joy Shi; Gernard Msamanga; Wafaie W Fawzi; Christopher R Sudfeld

doi:10.1093/jn/nxz246

The Effect of Maternal Multiple Micronutrient Supplementation on Female Early Infant Mortality Is Fully Mediated by Increased Gestation Duration and Intrauterine Growth

J Nutr. 2020 Feb 1;150(2):356-363. doi: 10.1093/jn/nxz246.

Authors

Mary K Quinn¹, Emily R Smith^{1

2}, Paige L Williams^{3

4}, Willy Urassa⁵, Joy Shi⁴, Gernard Msamanga⁶, Wafaie W Fawzi^{1

4

7}, Christopher R Sudfeld^{1

7}

Affiliations

¹ Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, MA, USA.
² Bill & Melinda Gates Foundation, Seattle, WA, USA.
³ Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, MA, USA.
⁴ Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA.
⁵ Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
⁶ Department of Community Health, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
⁷ Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.

Abstract

Background: Maternal micronutrient supplementation in pregnancy (MMS) has been shown to improve birth weight among infants in low- and middle-income countries. Recent evidence suggests that the survival benefits of MMS are greater for female infants compared to male infants, but the mechanisms leading to differential effects remain unclear.

Objective: The objective of this study was to examine the potential mechanisms through which MMS acts on infant mortality among Tanzanian infants.

Methods: We used data collected from pregnant women and newborns in a randomized, double-blind, placebo-controlled trial of MMS conducted in Tanzania to examine mediators of the effect of MMS on 6-wk infant mortality (NCT00197548). Causal mediation analyses with the counterfactual approach were conducted to assess the contributions of MMS on survival via their effects on birth weight, gestational age, weight-for-gestational age, and the joint effect of gestational age and weight-for-gestational age. The weighting method allowed for interaction between gestational age and weight-for-gestational age.

Results: Among 7486 newborns, the effect of MMS on 6-wk survival was fully mediated (100%) through the joint effect of gestational age and weight-for-gestational age. MMS was also found to have a significant natural indirect effect through increased birth weight (P-value < 0.001) that explained 75% of the total effect on 6-wk mortality. When analyses were stratified by sex, changes in gestational age and weight-for-gestational age fully mediated the mortality effect among female infants (n = 3570), but these mediators only explained 34% of the effect among males (n = 3833).

Conclusions: The potential sex-specific effects of MMS on mortality may be a result of differences in mechanisms related to birth outcomes. In the context of the Tanzanian trial, the observed effect of MMS on 6-wk mortality for female infants was entirely mediated by increased gestation duration and improved intrauterine growth, while these mechanisms did not appear to be major contributors among male infants.

Keywords: birth outcomes; infant mortality; maternal nutrition; mediation; multiple micronutrient supplementation.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adult
Dietary Supplements*
Female
Fetal Development*
Humans
Infant
Infant Mortality*
Micronutrients / administration & dosage*
Tanzania
Young Adult

Substances

Micronutrients

Associated data

ClinicalTrials.gov/NCT00197548

Grants and funding

T32 AI007358/AI/NIAID NIH HHS/United States